Linkage analysis of Charcot-Marie-Tooth neuropathy (HMSN type I)

Abstract

Fifteen HMSN families with 218 members and documented male-to-male transmission and slow motor nerve conduction velocities were informative for linkage to Duffy blood group (Fy), antithrombin III cDNA probe (AT3) and renin (REN). Our data support linkage to Fy in 8 families (lod score = 2.45 at θ = 0) consistent with HMSN type IB. Linkage to AT3 (lod score = 1.28 at θ = 0) and linkage of Fy to AT3 (lod score = 1.61 at θ = 0) is also supported in 3 of the 8 original families. Linkage to REN (lod score = 0.78 at θ = 0), linkage of Fy to REN (lod score = 0.89 at θ = 0), and linkage of AT3 to REN (lod score = 0.88 at θ = 0) is supported in only 2 of the 8 original families. Linkage to Fy was rejected in seven families, consistent with HMSN type IA (lod score = −4.34 at θ = 0.05). Linkage to AT3 was rejected in 12 families (lod score = −9.52 at θ = 0.05). Linkage to REN was rejected in 13 families (lod score = −11.07 at θ = 0.05). Our data provide support for the concept of genetic heterogeneity in CMT hypertrophic neuropathy (HMSN type I). The linkage of HMSN type IB to Fy seems to be tighter than to AT3 and REN, strongly suggesting the mapping of HMSN type IB locus on the proximal part of the long arm of chromosome 1, close to the centromere.